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The role of CHX10 in the development of the vertebrate retina

Rutherford, AD; (2002) The role of CHX10 in the development of the vertebrate retina. Doctoral thesis (PhD), UCL (University College London). Green open access

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Abstract

Complex interactions between intrinsic and extrinsic factors regulate the development of the retina from multipotential progenitor cells to the highly organised, mature tissue. Many genes are known to be essential to this process. Chx10 is a homeodomain transcription factor that is essential for the development of the retina and eye in many vertebrate species. Based on previous work embracing Chx10 gene expression patterns and the analysis of the mutant mouse Chx/r-JA'J, which has a null mutation in Chx10, the established roles of Chx10 in eye development include promotion of cellular proliferation in the neuroblastic retina, specification of bipolar interneurons in the differentiating retina, and maintenance of bipolar cells in the mature retina. In the first section of this thesis, I have explored the role of the human orthologue, CHX10, in the development of the eye, by examining gene expression patterns during embryonic human development. In a comparative study between the Chx/r-Jk'J and wild-type mouse, I have investigated the impact that the absence of Chx10 has on the expression of other genes that are required for normal eye development. Notably, the expression of the photoreceptor-specific transcription factor gene Crx is significantly delayed, which may lead to the observed photoreceptor phenotype in Chx/Gor'u'i. Chx10 is not expressed in photoreceptors, so, using a primary cell culture of Chx/r"'-v°r-J retinal neuroblasts, I investigated possible signalling mechanisms by which interactions between Chx10 and Crx could be fulfilled, and have demonstrated that retinoic acid may be capable in vitro of inducing expression of photoreceptor-specific genes in the absence of Chx10. In the final part of the thesis, I have identified, cloned and characterised a novel Chx10-like human cDNA, found as a fragment of an expressed sequence tag (EST) on Human Genome Project databases. Data presented here demonstrates that this putative novel gene is retinal specific, expressed in the adult retina, and maps to human Chromosome 20.

Type: Thesis (Doctoral)
Qualification: PhD
Title: The role of CHX10 in the development of the vertebrate retina
Open access status: An open access version is available from UCL Discovery
Language: English
URI: https://discovery.ucl.ac.uk/id/eprint/10057801
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